Variant 6-99435828-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001346022.3(USP45):c.2333A>G(p.Asn778Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,612,634 control chromosomes in the GnomAD database, including 801,562 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.98 ( 73770 hom., cov: 31)

Exomes 𝑓: 1.0 ( 727792 hom. )

Consequence

USP45
NM_001346022.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.74

Variant links:

Genes affected

USP45 (HGNC:20080): (ubiquitin specific peptidase 45) The protein encoded by this gene is a deubiquitylase that binds ERCC1, the catalytic subunit of the XPF-ERCC1 DNA repair endonuclease. This endonuclease is a critical regulator of DNA repair processes, and the deubiquitylase activity of the encoded protein is important for maintaining the DNA repair ability of XPF-ERCC1. [provided by RefSeq, Sep 2016]

USP45 links:

TSTD3 (HGNC:):

TSTD3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.8804E-7).

BP6

Variant 6-99435828-T-C is Benign according to our data. Variant chr6-99435828-T-C is described in ClinVar as [Benign]. Clinvar id is 1684198.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP45	NM_001346022.3 linkuse as main transcript	c.2333A>G	p.Asn778Ser	missense_variant	18/18	ENST00000500704.7	NP_001332951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP45	ENST00000500704.7 linkuse as main transcript	c.2333A>G	p.Asn778Ser	missense_variant	18/18	5	NM_001346022.3	ENSP00000424372	P1	Q70EL2-1
USP45	ENST00000327681.10 linkuse as main transcript	c.2333A>G	p.Asn778Ser	missense_variant	18/18	1		ENSP00000333376	P1	Q70EL2-1
USP45	ENST00000496518.6 linkuse as main transcript	c.*1299A>G		3_prime_UTR_variant, NMD_transcript_variant	13/13	1		ENSP00000421248
USP45	ENST00000369233.6 linkuse as main transcript	c.2189A>G	p.Asn730Ser	missense_variant	17/17	5		ENSP00000358236

Frequencies

GnomAD3 genomes

AF:

0.984

AC:

149742

AN:

152188

Hom.:

73715

Cov.:

show subpopulations

Gnomad AFR

AF:

0.944

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.994

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.987

GnomAD3 exomes

AF:

0.996

AC:

248587

AN:

249602

Hom.:

123810

AF XY:

0.997

AC XY:

134598

AN XY:

134976

show subpopulations

Gnomad AFR exome

AF:

0.942

Gnomad AMR exome

AF:

0.998

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.999

GnomAD4 exome

AF:

0.998

AC:

1457881

AN:

1460328

Hom.:

727792

Cov.:

AF XY:

0.999

AC XY:

725427

AN XY:

726428

show subpopulations

Gnomad4 AFR exome

AF:

0.939

Gnomad4 AMR exome

AF:

0.998

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.996

GnomAD4 genome

AF:

0.984

AC:

149857

AN:

152306

Hom.:

73770

Cov.:

AF XY:

0.984

AC XY:

73314

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.944

Gnomad4 AMR

AF:

0.994

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.987

Alfa

AF:

0.996

Hom.:

151817

Bravo

AF:

0.981

TwinsUK

AF:

0.999

AC:

3706

ALSPAC

AF:

1.00

AC:

3853

ESP6500AA

AF:

0.938

AC:

4132

ESP6500EA

AF:

1.00

AC:

8599

ExAC

AF:

0.995

AC:

120784

Asia WGS

AF:

0.997

AC:

3467

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Leber congenital amaurosis 19

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.3

DANN

Benign

0.83

DEOGEN2

Benign

0.00077

T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.055

.;T;T

MetaRNN

Benign

6.9e-7

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.6

N;N;.

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

0.86

N;N;N

REVEL

Benign

0.075

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.90

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.0050

MPC

0.070

ClinPred

0.00092

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.025

gMVP

0.072

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over